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Identification and biological activities of a new antiangiogenic small molecule that suppresses mitochondrial

Ki Hyun Kim1, Ju Yeol Park, Hye Jin Jung

  • 1Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.

Biochemical and Biophysical Research Communications
|December 15, 2010
PubMed

Insights

Researchers identified YCG063, a novel small molecule that inhibits angiogenesis by suppressing mitochondrial reactive oxygen species (ROS) generation, particularly under hypoxic conditions. This discovery offers a new tool for studying diseases linked to angiogenesis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Mitochondrial reactive oxygen species (ROS) play crucial roles in cellular functions.
  • Elevated mitochondrial ROS in hypoxic cells are implicated in angiogenesis-related diseases like cancer and ischemic disorders.

Purpose of the Study:

  • To identify and characterize a novel small molecule inhibitor of angiogenesis.
  • To investigate the mechanism of action focusing on mitochondrial ROS suppression.

Main Methods:

  • Phenotypic cell-based screening using an ArrayScan HCS reader to identify small molecules.
  • In vitro assays for angiogenic tube formation and chemoinvasion.
  • In vivo angiogenesis assay using the chorioallantoic membrane (CAM).
  • Western blot analysis for HIF-1α and VEGF expression.

Main Results:

  • YCG063 was identified as an inhibitor that suppresses mitochondrial ROS generation in a dose-dependent manner under hypoxia.
  • YCG063 significantly inhibited in vitro angiogenesis (tube formation, chemoinvasion) and in vivo angiogenesis (CAM assay) at non-toxic concentrations.
  • YCG063 decreased the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and its target gene vascular endothelial growth factor (VEGF).

Conclusions:

  • A novel anti-angiogenic small molecule, YCG063, was discovered that targets mitochondrial ROS.
  • YCG063 demonstrates therapeutic potential for angiogenesis-driven diseases by inhibiting ROS and downstream signaling pathways.
  • This compound serves as a valuable tool for further research into hypoxia-driven angiogenesis.

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